Developing RNA Vaccines to Treat Peanut Hypersensitivity

开发治疗花生过敏的 RNA 疫苗

• 批准号: 10570339
• 负责人: Herman F Staats
• 金额: $ 26.08万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-03 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570339
• 关键词: 2019-nCoV; Address; Adjuvant; Affect; Allergen Immunotherapy; Allergens; Allergic; Allergic Disease; Allergic Reaction; Allergy to peanuts; Anaphylaxis; Antibodies; Antigens; CD8-Positive T-Lymphocytes; COVID-19 pandemic; Cell Degranulation; Clinical; Communicable Diseases; Data; Developed Countries; Development; Dose; Epitopes; Event; Exposure to; FDA approved; Food Hypersensitivity; Formulation; Foundations; Future; Generations; Goals; Human; Hypersensitivity; IgE; IgG(T); Immunization; Immunize; Immunoglobulin A; Immunoglobulin G; Immunotherapeutic agent; Immunotherapy; In Vitro; Individual; Inflammation Mediators; Length; Life; Mediating; Medical; Messenger RNA; Methods; Monitor; Mus; Mutate; Mutation; Nose; Oral; Oral Administration; Package Insert; Persons; Population; Prevalence; Product Approvals; Production; Protein Truncation; Proteins; RNA; RNA vaccine; Research; Risk Reduction; Route; Safety; Serum; Severities; Surface; Symptoms; T cell response; T-Lymphocyte; T-Lymphocyte Epitopes; Technology; Testing; Time; Transfection; Vaccine Production; Vaccines; Western Blotting; allergic response; cell mediated immune response; coronavirus disease; crosslink; desensitization; granulocyte; immunogenicity; improved; in vivo; mast cell; mutant; natural hypothermia; oral immunotherapy; prevent; protein expression; response; vaccine platform

Project Summary/Abstract: Oral immunotherapy with PALFORZIA® is a recently FDA-approved therapy to treat peanut allergy. This therapy requires daily doses of characterized peanut proteins administered orally to peanut hypersensitive individuals. A major limitation of the PALFORZIA® therapy is the potential for the onset of allergic responses and possibly anaphylaxis due to activation of peanut-specific IgE coated mast cells. Development of hypoallergenic peanut proteins devoid of IgE-mediated granulocyte activation potential may address the known safety limitations of therapy with PALFORZIA®. The rise of the SARS-CoV-2 pandemic and rapid production and dissemination of mRNA COVID vaccines has highlighted the benefits of mRNA vaccines to protect against infectious diseases. The goal of this project is to utilize mRNA vaccine technology to express peanut proteins that lack and/or disrupt known IgE epitopes to provide a peanut allergen vaccine that does not induce allergic reactions in hosts hypersensitive to the native allergen. This proposal will utilize the dominant peanut allergen, Ara h 2, which is recognized by majority of peanut allergic individuals and is sufficient to induce hypersensitivity in mice, to develop mRNA vaccines that produce native Ara h 2 or mutant Ara h 2 with mutations in known linear IgE epitopes. The studies described in this proposal will evaluate in vitro protein production, in vitro IgE-mediated granulocyte activation, in vivo immunogenicity, and in vivo allergic disease activation in hosts sensitized to the native allergen. The results from this proposal will generate proof-of-concept preliminary data to support future studies to develop mRNA vaccines expressing multiple peanut proteins to treat peanut- hypersensitivity in allergic hosts.

项目摘要/摘要：PALFORZIA®口服免疫疗法是最近FDA批准的一种治疗方法， 治疗花生过敏。这种疗法需要每天口服给予一定剂量的特征性花生蛋白， 花生过敏的人。PALFORZIA®治疗的一个主要局限性是潜在的发作 过敏反应和可能的过敏反应，由于激活花生特异性IgE包被的肥大细胞。 开发缺乏IgE介导的粒细胞活化潜力的低变应原性花生蛋白可能 解决了已知的PALFORZIA®治疗的安全性局限性。SARS-CoV-2大流行的兴起， mRNA COVID疫苗的快速生产和传播凸显了mRNA疫苗的益处 来预防传染病。本项目的目的是利用mRNA疫苗技术， 缺乏和/或破坏已知IgE表位的花生蛋白，以提供不 在对天然过敏原过敏的宿主中诱发过敏反应。该提案将利用主导 花生过敏原，Ara h 2，它被大多数花生过敏个体所识别，并足以诱导 小鼠超敏反应，以开发产生天然Ara h 2或突变Ara h 2的mRNA疫苗 已知的线性IgE表位。本提案中描述的研究将评估体外蛋白质生产， 体外IgE介导的粒细胞活化、体内免疫原性和宿主体内过敏性疾病活化 对天然过敏原敏感该提案的结果将产生概念验证的初步数据 以支持未来的研究，开发表达多种花生蛋白的mRNA疫苗来治疗花生- 过敏宿主的超敏反应。